Multi-walled carbon nanotubes injure the plasma membrane of macrophages
Multi-walled carbon nanotubes injure the plasma membrane of macrophages
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DOI：
10.1016/j.taap.2008.06.016
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发表时间：
2008-10-15
影响因子：
3.8
通讯作者：
Furuyama, Akiko
中科院分区：
文献类型：
--
作者：
Hirano, Seishiro;Kanno, Sanae;Furuyama, Akiko
碳纳米管(CNTs)是一种新兴的纳米技术材料，有望在不久的将来大规模生产。然而，在大规模生产之前，应该首先解决某些与健康有关的问题。例如，当吸入碳纳米管时，其纤细的形状和生物持久性特征可能会导致肺部疾病，其方式类似于石棉。在本研究中，将高纯度多壁碳纳米管(MWCNTs，67 nm)和UICC青石棉暴露于小鼠巨噬细胞J774.1)，以评价这些纳米纤维的毒性。多壁碳纳米管的细胞毒性高于青石棉。抗氧化剂N-乙酰半胱氨酸和谷胱甘肽合成抑制剂丁硫氨酸亚磺胺不影响多壁碳纳米管的毒性作用。基因芯片分析表明，MWCNTs的细胞毒性不能用基因表达的增加或减少来解释，尽管MWCNTs使某些细胞因子的mRNA水平略有增加。此外，多壁碳纳米管不能显著激活ERK、JNK和p38等MAP激酶，也不能激活caspase 3和PARP等常见的细胞凋亡通路。电子显微镜研究表明，多壁碳纳米管结合在巨噬细胞的质膜上，破坏质膜的完整性。当MWCNT暴露的巨噬细胞被轻轻裂解时，发现几种蛋白质吸附在MWCNT上。其中一种是具有胶原性结构的巨噬细胞受体(MARCO)。MARCO基因转染组CHO-K1细胞与多壁碳纳米管结合的速度快于模型转染组。这些结果表明，MWCNTs可能通过与质膜上的Marco反应，使质膜破裂，从而在吞噬细胞中触发细胞毒作用。(C)2008 Elsevier Inc.保留所有权利。
Carbon nanotubes (CNTs) are emerging nanotechnology materials which are likely to be mass-produced in the near future. However, prior to mass-production, certain health-related concerns should first be addressed. For example, when inhaled, the thin-fibrous shape and the biopersistent characteristics of CNTs may cause pulmonary diseases, in a manner similar to asbestos. In the present study, mouse macrophages J774.1) were exposed to highly-purified multi-walled CNTs (MWCNTs, 67 nm) or to UICC crocidolite in order to evaluate the toxicity of these nano-size fibers. The cytotoxicity of MWCNTs was found to be higher than that of crocidolite. The toxic effect of MWCNTs was not affected by N-acetylcysteine, an antioxiclant, or buthionine sulfoximine, a glutathione synthesis inhibitor. cDNA microarray analyses suggested that the cytotoxicity of MWCNTs could not be explained satisfactorily by either an increase or decrease of gene expression, although mRNA levels of some cytokines were slightly increased by MWCNTs. Moreover, MWCNTs did not significantly activate either MAP kinases such as ERK, JNK and p38, nor common apoptosis pathways such as caspase 3 and PARP. Electron microscopic studies indicated that MWCNTs associate with the plasma membrane of macrophages and disrupt the integrity of the membrane. Several proteins were found to adsorb onto MWCNTs when MWCNT-exposed macrophages were gently lysed. One of these proteins was macrophage receptor with collagenous structure (MARCO). MARCO-transfected CHO-K1 cells associated with MWCNTs more rapidly than mock-transfected cells. These results indicate that MWCNTs probably trigger cytotoxic effects in phagocytotic cells by reacting with MARCO on the plasma membrane and rupturing the plasma membrane. (C) 2008 Elsevier Inc. All rights reserved.